Bone cement containing coated radiopaque particles and its preparation

ABSTRACT

An acrylic radiopaque bone cement for orthopedic use comprises a solid phase composed of a mixture of at least one poly(methyl acrylate)-based polymer, one free-radical polymerization initiator and one or more substances opaque to X-rays, and a liquid phase substantially composed of a mixture of at least one monomer, one accelerator and one stabilizer. The radiopaque substances comprise metallic tungsten and tantalum particles, compounds or mixtures thereof, covered with a polymer coating compatible with said bone cement. The coating layer of the particles of radiopaque substances is an acrylic polymer based on poly(methyl methacrylate). The amount of radiopacifying element is between 1% and 20% by weight, relative to the solid phase, preferably between 2% and 5% by weight, relative to the solid phase. The solid phase may additionally comprise one or more pharmacologically active substances. The method for its preparation consists in preparing the radiopacifying material by coating the metal particles with a layer of a polymer which is compatible with the matrix and exhibits oxygen barrier properties such that said layer does not dissolve completely in the liquid phase so as to keep its oxygen barrier properties at least partly unchanged.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention relates to the field of bone cements andspecifically concerns a radiopaque acrylic bone cement having improvedmechanical characteristics and a method for its preparation.

The bone cement according to the invention is therefore suitable for useadvantageously in surgery where the combination of a high degree ofradiopacity and notable mechanical strength are required.

More particularly, the present invention relates to a bone cement whichis suitable in particular for applications in vertebroplasty,cranioplasty, maxillofacial surgery and for fixing prostheses inorthopaedic surgery.

2. Background Art

In the orthopaedic surgery sector, bone cements composed of a mixture ofresins biocompatible with the bone tissues are known and commonly usedfor stably fixing prostheses of different types in a wide range oflocations on the skeleton or for restoring the continuity of tissues.

The most commonly used resins belong to the acrylic materials. The morewidely used bone cements are composed of two phases, a liquid phasesubstantially composed of methyl methacrylate with an addition ofN,N-dimethyl-p-toluidine as accelerator and hydroquinone as stabilizer,and a solid phase composed of a dry powder substantially composed ofpoly(methyl methacrylate) with a peroxide, usually benzoyl peroxide, aspolymerization initiator. At the moment of use, the two phases aremixed, the polymer powder representing the solid phase is dissolved inthe monomer present in the liquid phase, giving a liquid viscoussolution. In the meantime, the N,N-dimethyl-p-toluidine causes theperoxide to decompose with the formation of free radicals which initiatethe polymerization reaction, resulting in hardening of the mixture.

In addition to poly(methyl methacrylate), bone cements are known whichcontain a solid phase containing resins of the poly(ethyl methacrylate),poly(butyl methacrylate), poly(methyl methacrylate/styrene) types and/orcopolymers thereof, which belong to the class of acrylic resins.

The effect of the bone cement consists in completely filling the voidspresent between the prostheses and the bone cavity prepared forimplantation thereof, so as to ensure mechanical anchoring and a perfectfit of the bone implant.

The mechanical strength of the hardened cement thus obtained is not ashigh as that of the original bone tissues. Indeed, as a result of theconsiderable loads or as a result of fatigue stress at a high cyclenumber, the bone cement fillings can give way and fracture. Themodification of such fillings with time, their eventual flaking-off andtheir mechanical weakening must therefore be able to be detected andmonitored, for example using standard radiological and tomographictechniques.

Since the synthetic base resin is transparent to X-rays, the bone cementmust be rendered opaque by adding suitable inorganic biocompatiblesubstances.

The opacity to X-rays of the elements increases substantially inproportion to their atomic weight. In general, especially for theheavier elements, their toxicity also increases. In medicine the knownand most commonly used contrast agents are iodine, either in elementalor bonded form, bismuth in the form of carbonate and barium in the formof sulphate.

By using compounds such as salts or oxides, the radiopaque elementconstitutes only a portion of the additive. For example, the metalamounts to only 58% of barium sulphate, the remaining material beingsubstantially transparent to X-rays.

In the known bone cements, such radiopacifying materials usually consistof barium sulphate or zirconium oxide additives, in an amount of about10% by weight, relative to the dry polymer.

Such additives, which introduce discontinuities in the polymer, weakenfurther the mechanical properties of the hardened cement, increasing therisk of failure and frequency of fracturing or flaking off.

With the aim of reducing such disadvantages, the teachings of U.S. Pat.No. 5,795,922 propose encapsulation of the radiopacifying substance, inthis case selected from the group consisting of barium salts, zirconiumoxide and bismuth glasses, in microcapsules of a compatible polymermaterial. During formation of the bone cement, the polymer materialdissolves completely in the liquid phase releasing its contents, theradiopaque substance, which is enveloped by the polymer being formed.

These known bone cements are not suitable for the treatment of certaindisorders, for example, in the case of vertebroplasty.

Indeed, in the case of disorders of the general tumour type, in which anemptying of the vertebra structure is produced, the latter loses itsmechanical strength and collapses under the body weight, resulting incrushing of the nerve endings, causing intense suffering of the patientand a partial loss of motor function.

At the present time, in accordance with the prior art hitherto, suchdisorders are treated with prostheses, metal plates or by administeringanalgesics.

A further known technique for such disorders consists in opening thevertebra, introducing the bone cement of the type described above, andclosing it again. The hardened bone cement substitutes the missing partof the vertebra.

Recently, a new technique has been proposed which consists in injectingliquid bone cement, by means of a needle, inside the vertebra, thusavoiding the invasive surgical intervention referred to above.

This technique requires the use of a low-viscosity liquid bone cement soas to be able to inject it easily by means of a needle which may have adiameter of even less than 2 mm.

This operation is complicated and not free of risks since an error inpositioning of the cement could result in a contact of the resin withthe nerve endings of the spinal column, resulting in a paralysis of thepatient or in a substantial increase in pain, owing to the insertion ofprotrusions in direct contact with the nerve centers which pass throughthe spinal column.

In order to be able to perform this operation with absolute safety, thesurgeon must be well-informed of the state of progress of the injection,which is controlled in real time by means of X-rays. Since the timeduring which monitoring must take place is quite long, usually severalhours, the intensity of exposure to the radiation must be extremely low.Accordingly, it is not possible to use radiological or tomographictechniques involving significant radiation doses, but insteadfluoroscopic techniques in which the patient is subjected tolow-intensity X-rays must be used.

The known bone cements described above, which are particularly suitablefor the fixing of prostheses, have proved to be insufficiently opaque tolow-intensity X-rays, poorly visible, practically transparent andsubstantially unsuitable for performing the injection with adequatesafety.

The medico-scientific literature has reported several cases in which thesurgeon has added an appreciable quantity of the radiopacifying contrastagent barium sulphate of up to 30–40% by weight, so as to render thecement used sufficiently radiopaque.

On the other hand, the use of a metal in the form of salt has theconsequence that only 58% by weight of the material introduced has anactual radiopacifying effect.

The presence of a voluminous quantity of powdery radiopacifier in theacrylic matrix increases the probability of initiating fractures andthus undermines the integrity of the structure and jeopardizes themechanical strength of the material in the long run (fatigue strength).This phenomenon is confirmed even in those cases in which the staticperformances comply with the minimum requirements of the ISO standard5833.

In any case, this benefits the patient, but the intervention cannotguarantee that the expected result will be maintained over a longperiod, since the reinforcing structure is extremely weak.

The medico-scientific literature has described other cases in which thesurgeon adds to the bone cement of the type described above containingapproximately 10% by weight of barium sulphate, relative to the drypolymer, or approximately 15% by weight of zirconium oxide, relative tothe dry polymer, a quantity of powdery tungsten amounting to about 2% byweight as further radiopacifier.

The addition of about 9% by weight of tantalum powder to a bone cementdevoid of radiopacifiers is likewise known.

In all abovementioned cases, the addition is made directly by thesurgeon, shortly before the intervention, under his responsibility andusing a non-certified material. This has made it possible to improve theradiopacifying effect without decreasing excessively the mechanicalproperties of the resulting acrylic cement.

Nevertheless, the latter bone cements have also proved to be not withoutdrawbacks. A first disadvantage is the fact that powdery tantalum, incontrast to tantalum in plaque form, is not considered biocompatibleaccording to current regulations. The biocompatibility of tantalum isrelated to oxygen absorption, a phenomenon which is increased by theconsiderable specific surface area of the finely divided form necessaryfor efficient dispersion in the acrylic cement. Even if the cement isprepared immediately before use, it is almost impossible to prevent theoxygen from being absorbed by the metal and to keep its level at valuesbelow 300 ppm as required by the current regulations (ISO 13782), andthe use of tantalum oxide is prohibited by the Pharmacopoeia.

A second drawback consists in the fact that the tantalum powder must beprepared by the surgeon at the moment of using it since, due to thesterility and biocompatibility requirements mentioned above, it ispractically impossible to purchase tantalum powder in sterile form onthe market.

A further drawback consists in the fact that it is difficult to obtain adiameter distribution of the particles forming the fine powder suitablefor injection by means of a syringe.

A further drawback consists in the fact that the dispersion phase of thetantalum powder has the tendency to form inclusions of air in the bonecement.

A further drawback consists in the fact that it is extremely difficultto obtain a homogeneous dispersion of the powder in the polymer matrix.

International Patent Publication No. WO-A-9204924 discloses a radiopaquebone cement comprising a solid phase of polymethylmethacrylate powderand a liquid phase of polymethylmethacrylate monomer, wherein added tothe solid phase are particles of radiopaque material coated withpolymethylmethacrylate before mixing with the liquid phase. Theradiopaque material is zirconium oxide or barium sulfate having diameterfrom 1 μm and 250 μm. However, the use of zirconium oxide or bariumsulfate as radiopaque materials does not permit improvement ofradiopacity combined with increased mechanical strength and fatigueresistance as specifically required for vertebroplasty. Moreover, thecoating layer applied to the radiopaque materials of this prior art isaimed at avoiding the porosity and non-uniformity of the cement andtherefore is not purported to prevent the formation of oxides.

International Patent Publication No. WO-A-9918894 discloses a bonecement specifically intended for vertebroplasty wherein the radiopaquematerial comprises particles of barium sulfate, tungsten or tantalum andtherefore exhibits higher radiopacity as compared with the known bonecement compositions. However, the surface of the tungsten and/ortantalum particles used in Publication No. WO-A-9918894 is free ofprotection and has no coating to prevent oxygen absorption, andaccordingly, some embodiments of this bone cement may be prohibited bythe Pharmacopoeia. Morover, WO-A-9918894 gives no indication of the formof protection of the tungsten and/or tantalum particles used asradiopacifying agent.

OBJECTS OF THE INVENTION

A general object of the present invention consists in eliminating thedrawbacks of the abovementioned prior art by providing an acrylic bonecement which exhibits improved radiopacity and mechanical strengthproperties.

A particular object is to provide an acrylic bone cement which hasimproved mechanical strength properties, in particular better fatiguebehavior, compared to the known bone cements of the past.

A particular object is to provide an acrylic bone cement which hasimproved radiopacity properties without the addition of additivesconsisting only in part of radiopacifiers.

Another particular object of the present invention is to provide aliquid acrylic bone cement, prepared with biocompatible materialswithout a reduction in biocompatibility.

A further object of the present invention is to provide a liquid acrylicbone cement, prepared in sterile fashion using a sterile or readilysterilizable material.

Another further object of the present invention is to provide an acrylicbone cement which is particularly suitable for vertebroplasty.

Yet Another object of the present invention is to provide a method forthe preparation of an acrylic bone cement which is relatively easy forthe surgeon to perform.

SUMMARY OF THE INVENTION

The aforementioned objects, together with others that will become moreapparent hereinafter, are achieved by means of a radiopaque acrylic bonecement for orthopaedic use that exhibits considerable radiopacity, whichis achieved by adding a limited amount of a radiopaque contrast agent.

Furthermore, the bone cement possesses mechanical properties which areconsiderably better than those of the prior art, in which the contrastelement is added, but not bonded to the polymer matrix and constitutesan initiating element for fracturing of the polymerized mass.

In the method for preparation of the bone cement, the polymer coatinglayer of the metal defines at the moment of polymerization a zone ofchemical adhesion between the polymer chains being formed and the metalparticles. This determines the increase in mechanical properties of thecomposite in which the metal particles are no longer an element which isnot bonded to the polymer matrix.

This makes it possible to take advantage of the higher ductility of themetallic material compared to the fragility of the polymer material,imparting to the composite as a whole better mechanical properties,especially a better tenacity and fatigue strength.

A further advantage of the bone cement according to the inventionconsists in the fact that the biocompatible and sterilizable polymercoating layer protects each single tantalum or tungsten metal particlecontained in the mixture from exposure to oxygen. This prevents theoxygen from being absorbed, thus avoiding the formation of oxides andovercoming the drawbacks and pharmacological limitations linked to thepresence of oxygen.

Even after addition of the solid phase to the liquid phase, thiscoating, owing to the fact that it is not dissolved completely, retainsits function as barrier and protector of the metal present therein.

Moreover, the bone cement can be delivered in the same package as thecontrast agent and added directly by the manufacturer to the solid phasein the optimum amount and diametral distribution for the desiredapplication as sterile medical remedy.

A further advantage of the invention is that it is possible to add tothe bone cement active substances, which will be released in-situ forthe treatment of possible disorders.

A further advantage of the bone cement according to the invention isthat it can be formulated with such a fluidity that it can beadministered through a cannula having an internal diameter of less than2 mm.

The device according to the present invention can advantageously be usedfor the filling of deep and critical bone holes by means of operationswith limited invasiveness, for example, using percutaneous techniques.Moreover, the use can be extended to zones in which high radiopacity andmechanical properties, not satisfied by the known bone cements, arerequired.

Using the radiopaque acrylic bone cement according to the invention itis possible, for example, to perform vertebroplasty interventions underabsolutely safe conditions, with continuous monitoring of the operation,achieved by administering to the patient a limited amount of X-rays andobtaining a hardened support having considerable mechanical strengthwith respect to the stresses induced during walking.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features and advantages of the invention will be more clearlyunderstood from the detailed description of several preferred, but notexclusive embodiments of the radiopacified acrylic bone cements,furnished by way of a non-limiting example, with reference to theaccompanying drawings, in which:

FIG. 1 shows a schematic representation of the bone cement;

FIG. 2 shows a partially sectioned view of a radiopaque metal particlecoated with a poly(methyl methacrylate)-based protective polymer;

FIG. 3, FIG. 4 and FIG. 5 show SEM (Scanning Electron Microscope)pictures of different amplification, i.e., 1000×, 3000× and 10,000×respectively, of the radiopaque tantalum metal particles as obtainedbefore being coated with the protective polymer; and

FIG. 6 and FIG. 7 show SEM (Scanning Electron Microscope) pictures ofdifferent amplifications, i.e., 3000× and 10,000×, respectively, of theradiopaque tantalum metal particles coated with protective polymer.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A radiopaque acrylic bone cement for orthopaedic use according to theinvention essentially comprises a solid phase dissolved in a liquidphase.

The solid phase is essentially composed of a mixture of at least oneacrylic polymer, for example based on poly(methyl methacrylate), atleast one free-radical polymerization initiator and at least one or moresubstances which are opaque to X-rays. More specifically, the mixturecan contain poly(methyl methacrylate), poly(methylmethacrylate/styrene), poly(butyl methacrylate) and copolymers thereofand benzoyl peroxide as initiator. Moreover, the solid-phase mixture maycontain one or more pharmacologically active substances.

The liquid phase is essentially composed of a mixture of a monomer, atleast one accelerator and at least one stabilizer. More specifically,the monomer can consist of monomethylmethacrylate and the acceleratorcan consist of N,N-dimethyl-p-toluidine.

Referring to FIG. 1, the hardened bone cement, indicated overall by 1,is composed of a polymer matrix 2 in which irregularly shaped particles3 composed of radiopaque elements 4 coated with a polymer compatiblewith the polymer matrix 2 are dispersed homogeneously.

The irregularly shaped particle 3, shown schematically in FIG. 2, iscomposed of the radiopaque element 4 completely coated with a polymerlayer 5 compatible with the matrix 2 and having such a thickness 6 thatit does not dissolve completely in the liquid phase duringpolymerization.

A particular characteristic of the present invention consists in addingradiopaque elements of high molecular weight, greater than 130 Dalton,in the form of metals, mixtures of metals, or metal compounds such asalloys. Indeed, many elements of high atomic weight, for example morethan 125 Dalton, are highly radiopaque and thus suitable for use as longas they are non-toxic or can be used in non-toxic form.

Preferably, the radiopaque substances contained in the solid phasecomprise tungsten and/or tantalum particles in the form of metals,compounds or mixtures thereof, which particles are covered with acoating layer of a polymer compatible with said bone cement. In place oftantalum or tungsten, it is also possible to use other metals of highatomic weight such its gold, platinum, bismuth or lead.

Ideally the coating layer of the particles is an acrylic polymer basedon poly(methyl methacrylate).

Advantageously, the coating layer can be obtained by adding the polymerbased on poly(methyl methacrylate), dissolved in a water-misciblesolvent, to an aqueous dispersion of the metal particles from which thesurface layer had previously been removed, followed by evaporation ofthe solvents and drying of said layer.

The oxygen content of the tantalum metal is preferably less than about300 ppm.

The diameter of the radiopaque particles coated with poly(methylmethacrylate) can be between 1 μm and 150 μm.

Before depositing the coating, the diameter of radiopacifying metalparticles can be between 1 μm and 100 μm.

Prior to the deposition of the coating, the radiopacifying particles canhave nanometer size, for example, a diameter between 25 nanometres and1000 nanometres. In this manner, the diameter of the coatedradiopacifying particles, which have a plurality or an aggregate ofnanometer-sized metal particles, can be between 20 μm and 60 μm, withthe noteworthy advantage of a more homogeneous and easier dispersion ofsaid particles in the polymer powder.

Ideally said nanometer-sized metal particles may have beenpre-sinterized.

Preferably, the tantalum or tungsten to poly(methyl methacrylate) weightratio in the particles is between 95/5 and 70/30.

The molecular weight of the particle coating polymer can advantageouslybe between 20,000 and 800,000 Dalton.

The amount of radiopacifying element can advantageously vary between 1%and 20% by weight, relative to the solid phase, and is preferablybetween 2% and 5% by weight, relative to the solid phase.

Advantageously, the solid phase and the coated radiopaque particles canbe contained in the same package. Alternatively, the solid phase and thecoated radiopaque particles can be contained in different packages.

In the case of a single package, it can consist of a shell containingboth the solid phase and the liquid phase. In clinical use, thecement-containing shell is opened, and its contents consisting of anenvelope containing the powder and the vial containing the liquid phaseis transferred to the operating room aseptically on a sterile shelf.

In preparing the cement, the ampule is opened, and the entire liquid isplaced in the mixing bowl, and all the powder is introduced into theliquid. In order to minimize the inclusion of bubbles, the cement mustbe mixed by moving the spatula from the outside to the center of thebowl. Since the whole powder must be impregnated with liquid, any solidresidues not impregnated with liquid are carefully immersed in the moistmass using the spatula.

At this point, the liquid mass can be transferred into a syringe forin-situ injection.

The radiopacifying powder according to the present invention can bemixed with the solid phase of the bone cement system.

Table 1 shows a few indicative but not exhaustive examples of preferredformulations.

TABLE 1 Liquid phase Solid phase (Values in (Values in percent byweight) percent by weight) Cemex RX Methyl 98.20 Poly(methyl 88.00(reference) methacrylate methacrylate) N,N-dimethyl- 1.80 Benzoyl 3.00p-toluidine peroxide Hydroquinone 75 ppm Barium 9.00 sulphate FU CemexXL Methyl 98.20 Poly(methyl 85.00 (reference) methacrylate methacrylate)N,N-dimethyl- 1.80 Benzoyl 3.00 p-toluidine peroxide Hydroquinone 75 ppmBarium 12.00 sulphate FU Example 1 Methyl 98.20 Poly(methyl 82.5(reference) methacrylate methacrylate) N,N-dimethyl- 1.80 Benzoyl 3.00p-toluidine peroxide Hydroquinone 75 ppm Barium 12.00 sulphate FUTantalum 2.50 as-delivered Example 2 Methyl 98.20 Poly(methyl 67.00(reference) methacrylate methacrylate) N,N-dimethyl- 1.80 Benzoyl 3.00p-toluidine peroxide Hydroquinone 75 ppm Barium 30.00 sulphate FUExample 3 Methyl 98.20 Poly(methyl 82.00 methacrylate methacrylate)N,N-dimethyl- 1.80 Benzoyl 3.00 p-toluidine peroxide Hydroquinone 75 ppmBarium 10.00 sulphate FU PMMA-coated 5.00 tantalum Example 4 Methyl98.20 Poly(methyl 82 methacrylate methacrylate) N,N-dimethyl- 1.80Benzoyl 3.00 p-toluidine peroxide Hydroquinone 75 ppm Barium 12.50sulphate FU PMMA-coated 2.50 tantalum Example 5 Methyl 98.20 Poly(methyl87 methacrylate methacrylate) N,N-dimethyl- 1.80 Benzoyl 3.00p-toluidine peroxide Hydroquinone 75 ppm PMMA-coated 10.00 tantalumExample 6 Methyl 98.20 Poly(methyl 82 methacrylate methacrylate)N,N-dimethyl- 1.80 Benzoyl 3.00 p-toluidine peroxide Hydroquinone 75 ppmZirconium 10.00 oxide PMMA-coated 5.00 tantalum Example 7 Methyl 98.20Poly(methyl 80 methacrylate methacrylate) N,N-dimethyl- 1.80 Benzoyl3.00 p-toluidine peroxide Hydroquinone 75 ppm Zirconium 14.50 oxidePMMA-coated 2.50 tantalum Example 8 Methyl 98.20 Poly(methyl 86methacrylate methacrylate) N,N-dimethyl- 1.80 Benzoyl 3.00 p-toluidineperoxide Hydroquinone 75 ppm Barium 8.50 sulphate FU PMMA-coated 2.50tungsten Example 9 Methyl 98.20 Poly(methyl 82.00 methacrylatemethacrylate) N,N-dimethyl- 1.80 Benzoyl 3.00 p-toluidine peroxideHydroquinone 75 ppm Barium 10.00 sulphate FU PMMA-coated 5.00 tungstenExample 10 Methyl 98.20 Poly(methyl 82 methacrylate methacrylate)N,N-dimethyl- 1.80 Benzoyl 3.00 p-toluidine peroxide Hydroquinone 75 ppmBarium 12.50 sulphate FU PMMA-coated 2.50 tungsten

Using the bone cements prepared by the abovementioned methodology andthe formulations listed in Table 1, in accordance ISO standard 5833,ASTM standard F451-99 and ISO standard 527, a few samples were preparedfor measuring the compressive strength, the tensile strength, thebending strength and the work at break. The latter, expressed in MJ/m³,is calculated as the integral of the stress/deformation curve obtainedin the bending test.

Tables 2, 3 and 4 list the values, expressed in MPa, obtained with thesamples.

TABLE 2 Standard Tensile Standard Compression deviation strengthdeviation Cemex RX 106 7.75 36 4.20 (reference) Example 1 108 3.51 381.04 Example 3 131 6.68 44 0.14 ISO 5833 >70 >30* *Limit not present inthe regulations

TABLE 3 Standard Modulus of Standard Bending deviation Elasticitydeviation Cemex RX 61 4.78 2974 64 (reference) Example 1 62 2.09 2850334 Example 3 70 5.19 2909 102 ISO 5833 >50 >1800

TABLE 4 Deformation at Standard Work at break Standard break (%)deviation (MJ/m³) deviation Cemex RX 2.01 0.17 0.88 0.14 (reference)Example 2 2.22 0.23 0.79 0.22 Example 3 2.72 0.39 1.11 0.31

The tests were carried out at ambient temperature and humidity. Thesamples, prepared according to ISO 5833, were kept in water at 37° C.for 48 hours, taken out a few minutes prior to the test and deformed ata set speed of 20 mm/min for the compression measurements, 10 mm/min forthe tensile measurements, and 5 mm/min for the bending stressmeasurements.

The work at break of the bone cement according to the present inventionshows an increase of 26%, relative to the value of conventional bonecement and of 40%, compared to the bone cement made radiopaque byaddition of a vast amount (30%) of barium sulphate.

Using the bone cements prepared by the abovementioned methodology andthe formulations listed in Table 1, the values of the chemical andphysical properties such as viscosity, flow behavior, doughing time,setting time and the maximum polymerization temperature were measuredaccording to ISO standard 5833:92 and ASTM standard F451-99. The valuesobtained are listed in Tables 5 and 6.

TABLE 5 Doughing Setting Viscosity time time Maximum η'₄ (DT) (ST)temperature (Pa*s) (min) (min) (° C.) Cemex XL 13,900 ± 2970   4′55″  12′50″ 64 Example 4 27,000 ± 1414   9′30″   16′00″ 72 ISO 5833 <5′<15′ <90

The value η′₄, of the apparent dynamic viscosity at 4′ from mixing,measured at 22° C. and a humidity of 32%, is customarily taken as adescriptive parameter of the rheological behavior of the material.

The measurements of DT, ST and the maximum polymerization temperaturewere performed in a laboratory temperature-controlled at 23° C.±1 and ata relative humidity greater than 40%, using material which, in turn, wasleft in a thermostat under the same conditions for at least 16 hours.

TABLE 6 Flow behaviour Standard % by (g) deviation weight Cemex XL 60.50.70 89 Example 4 58 85

The flow behavior represents the mass of cement, expressed in grams,which flows from the inclined mixing bowl at 90° C. in 60 seconds after1′ and 30″ from the beginning of mixing.

The bone cement according to the present invention exhibits very highproperties in all stress directions, and in particular the metaladditive improves the compressive strength.

In all cases, the materials have exceeded the limits required by theregulations and thus, from a mechanical point of view, fall entirelywithin the class of bone cements.

The polymerization temperature is increased in the tantalum materialeven though it is still substantially below the values required by thestandards.

It must be pointed out that the bone cement according to the inventioncan advantageously be used for surgical interventions in vertebroplastyby means of percutaneous in-situ injection of the cement or else forsurgical interventions of osteosynthesis in which superior radiopacityand mechanical properties are required.

1. Radiopaque acrylic bone cement for orthopedic use, comprising a solidphase essentially composed of a powder of at least one acrylic polymer,one free-radical polymerization initiator and one radiopacifyingmaterial, and a liquid phase substantially composed of a mixture of atleast one monomer, one accelerator and one stabilizer, said solid phasebeing capable of hardening upon mixing thereof with said liquid phase soas to give a bone cement matrix, wherein said radiopacifying materialcomprises particles of metals having molecular weight equal to or higherthan 130 Dalton, mixtures, alloys or compounds thereof, which particlesare covered with a coating layer of a polymer which is compatible withsaid matrix, wherein said metal particles comprise tantalum and/ortungsten particles, said polymer coating layer covering each of saidmetal particles to protect them from exposure to oxygen, said coatinglayer being so sized that it does not completely dissolve in said liquidphase during polymerization of said bone cement so as to keep its oxygenbarrier properties.
 2. Acrylic bone cement according to claim 1, whereinsaid metals of high molecular weight are selected in such a way as tohave an oxygen content of less than 300 ppm by weight.
 3. Acrylic bonecement according to claim 1, wherein said coating layer of said metalparticles is a polymer taken from the group consisting of poly(methylmethacrylate), poly(methyl methacrylate/styrene), poly(butylmethacrylate) and copolymers thereof.
 4. Acrylic bone cement accordingto claim 1, wherein each single uncoated metal particle has an averagediameter of between 1 μm and 100 μm.
 5. Acrylic bone cement according toclaim 1, wherein each single coated metal particle has an averagediameter of between 1 μm and 150 μm.
 6. Acrylic bone cement according toclaim 1, wherein said polymer coating layer covers an aggregate ofpreviously synthesized nanometer-sized metal particles.
 7. Acrylic bonecement according to claim 6, wherein said metal particles of saidaggregate have an average diameter of between 25 nm and 1000 nm. 8.Acrylic bone cement according to claim 1, wherein the molecular weightof the coating polymer of said particles which is compatible with saidbone cement is between 20,000 and 800,000 Dalton.
 9. Acrylic bone cementaccording to claim 1, wherein the molecular weight of the coatingpolymer of said particles which is compatible with said bone cement isbetween 300,000 and 800,000 Dalton.
 10. Acrylic bone cement according toclaim 1, wherein the weight ratio between the metal contained in saidparticles and their coating polymer is between 95:5 and 70:30. 11.Acrylic bone cement according to claim 1, wherein the amount of theradiopacifying material is between 1% and 20% by weight, relative tosaid solid phase.
 12. Acrylic bone cement according to claim 11, whereinthe amount of radiopacifying material is between 2% and 5% by weight,relative to said solid phase.
 13. Acrylic bone cement according to claim1, wherein said solid phase further comprises one or morepharmacologically active substances.
 14. Acrylic bone cement accordingto claim 1, wherein said solid phase and said coated radiopaqueparticles are contained in the same package.
 15. Acrylic bone cementaccording to claim 1, wherein said solid phase and said coatedradiopaque particles are contained in separate packages.
 16. Acrylicbone cement according to claim 1, wherein said at least one acrylicpolymer is taken from the group consisting of poly(methyl methacrylate),poly(methyl methacrylate/styrene), poly(butyl methacrylate) andcopolymers thereof.
 17. Method for preparing a radiopaque acrylic bonecement for orthopedic use, comprising the steps of: preparing a solidphase essentially composed of a powder of at least one acrylic polymer,one free-radical polymerization initiator and one radiopacifyingmaterial; preparing a liquid phase composed of a mixture of at least onemonomer, one accelerator and one stabilizer; mixing said solid phasewith said liquid phase so as to perform polymerization in such a waythat a bone cement matrix is obtained; and wherein the radiopacifyingmaterial is obtained by preparing a powder of metal particles ofmolecular weight equal or higher than 130 Dalton, mixtures, alloys orcompounds thereof, said metal particles comprising tantalum and/ortungsten particles, and coating said particles with a layer of a polymerwhich is compatible with said matrix, said polymer coating layer beingso selected to protect said metal particles from exposure to oxygen,said polymer coating layer being so sized that it does not completelydissolve in said liquid phase so as to keep its oxygen barrierproperties.
 18. Method according to claim 17, wherein said metalparticles, before being coated, are subjected to a step of removal oftheir surface layer.
 19. Method according to claim 17, wherein saidcoating layer of said metal particles is obtained by adding saidpolymer, dissolved in water-miscible organic solvents, to an aqueousdispersion of said radiopaque particles, followed by evaporation anddrying of said solvents.
 20. Method according to claim 17, wherein saidat least one acrylic polymer is taken from the group consisting ofpoly(methyl methacrylate), poly(methyl methacrylate/styrene), poly(butylmethacrylate) and copolymers thereof.